Multimodal imaging in hepatic epithelioid angiomyolipoma: a case report

Introduction

Hepatic epithelioid angiomyolipoma (HEAML) is a rare mesenchymal neoplasm that can occasionally exhibit malignant behavior, such as postoperative recurrence or distant metastasis. It belongs to the family of perivascular epithelioid cell tumors (PEComas) (1). Most HEAML patients are female, with lesions typically being solitary and predominantly located in the right lobe of the liver (2). Most patients are initially asymptomatic, and the lesions are typically discovered incidentally during routine physical exams. However, due to similarities in imaging findings, HEAML is often misdiagnosed as hepatocellular carcinoma (HCC), focal nodular hyperplasia (FNH) and hepatocellular adenoma (HA). The misdiagnosis rate is notably high, with a diagnostic accuracy rate of less than 32% (3). Herein, we present a case of HEAML in an elderly woman with mild fatty liver. We aim to utilize a multimodal imaging approach and review the literature to discuss the imaging features of HEAML, which may aid in establishing an accurate diagnosis. We present this case in accordance with the CARE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-837/rc).

Case presentation

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

A 69-year-old woman presented with occasional right upper abdominal distension and discomfort, with imaging examinations revealing an ovoid liver mass. The patient’s overall health status was good, with no history of chronic diseases such as hypertension, coronary heart disease, or diabetes. Additionally, there was no history of hepatitis, tuberculosis, food or drug allergies, surgical trauma, or blood transfusions. Laboratory examination results were within normal limits, with negative findings for carcinoembryonic antigen and AFP.

The axial image from the upper abdominal plain computed tomography (CT) scan revealed a local mass with isodense or slightly low density (50 Hounsfield units) in the S6 segment (Figure 1A), measuring approximately 43 mm × 27 mm. The lesion exhibited a vaguely defined border and was adjacent to the liver capsule, with no apparent expansion or depression in the local liver capsule. During the contrast-enhanced scan in the arterial phase, the mass demonstrated avid enhancement (116 Hounsfield units), with clearly visible short strip vascular enhancement within the lesion (Figure 1B). The enhanced lesion appeared wedge-shaped, with an increased range compared to the plain CT scan. In the venous phase, the enhancement of the lesion slightly diminished (104 Hounsfield units) (Figure 1C). Subsequently, during the delay phase, the enhancement was relatively moderate (84 Hounsfield units) but was unclearly displayed, indicating a wash-in and slow-out strengthening mode (Figure 1D). For further clarity of the short strip vascular enhancement within the lesion, maximal intensity projection (MIP) images were utilized during the arterial phase (Figure 1E,1F). Notably, there was no evidence of hemorrhage, necrosis, cystic degeneration, fatty degeneration, or calcification on the CT scan. Additionally, no fibrous scar enhancement was observed within the lesion.

Figure 1 The CT characteristics of HEAML. (A) The plain CT image reveals an ovoid mass in the S6 segment of the liver (black arrow). (B) In the arterial phase, the tumor exhibits significant enhancement with a short strip vessel (red arrow). (C) The lesion shows slightly diminished enhancement in the portal phase. (D) In the delay phase, the enhancement is relatively moderate. (E,F) Short strip vascular enhancement (red arrow) within the lesion is clearly depicted in the MIP images. The black arrows indicate the location of the lesion. CT, computed tomography; HEAML, hepatic epithelioid angiomyolipoma; MIP, maximal intensity projection.

The lesion exhibited hypointensity on T1-weighted images (Figure 2A), while displaying heterogeneous hyperintensity on T2-weighted images (Figure 2B), with discontinuous circular hyperintense signals visible at the lesion’s edge. On hepatic arterial phase, the lesion exhibited clear enhancement within the liver (Figure 2C), followed by diminished enhancement in the portal and delay phases, with a halo sign apparent around the lesion (Figure 2D,2E). As for diffusion-weighted imaging (DWI), uneven hyperintensity was observed within the lesion (Figure 2F).

Figure 2 The MRI characteristics of HEAML. (A,B) MRI shows hypointensity on T1-weighted and heterogeneous hyperintensity on T2-weighted images, with discontinuous circular hyperintense signals visible at the edge of the lesion (red arrow). (C-E) Contrast-enhanced MRI demonstrates hyperintensity on the arterial phase. On portal venous and delayed phase T1-weighted images, the lesion exhibits diminished enhancement. The halo sign is apparent around the lesion (red arrow). (F) Uneven hyperintensity is observed on DWI. The white arrows indicate the location of the lesion. DWI, diffusion weighted imaging; HEAML, hepatic epithelioid angiomyolipoma; MRI, magnetic resonance imaging.

The signal of out-phase was similar to in-phase, with no obvious attenuation observed (Figure 3A,3B). On hepatobiliary phase (HBP), the lesion exhibited hypointensity relative to the liver parenchyma (Figure 3C). Additionally, we used iterative decomposition of water and fat with echo asymmetry and least squares estimation quantification sequence (IDEAL IQ) to assess iron deposition and fat composition within the mass. R2* (Figure 3D) showed marginal hyperintensity on the lesion, with a maximum value of approximately 312.33 s⁻¹. As for fat fraction, the measured value for the liver parenchyma was 9.45%, while it was 2.95% for the lesion.

Figure 3 The MRI characteristics of HEAML. (A,B) The signal of the out-phase is similar to the in-phase. (C) The lesion shows hypointensity relative to the liver parenchyma on HBP. (D) R2* shows marginal hyperintensity on the lesion. The white arrows indicate the location of the lesion. HBP, hepatobiliary phase; HEAML, hepatic epithelioid angiomyolipoma; MRI, magnetic resonance imaging.

The patient underwent early laparoscopic liver tumor resection. A surgical biopsy of the lesion revealed that the tumor was composed of epithelioid cells with abundant, eosinophilic, or clear cytoplasm, and no lipomatous component was identified. Pathologically, dilated lymphatic vessels were observed, and an increased number of capillaries within the lesion indicated a rich blood supply (Figure 4). Immunohistochemistry staining demonstrated strong positivity for Melan-A, smooth muscle actin, and homatropine methylbromide-45 (HMB-45), while stains for S-100, Hepatocyte, and Desmin were negative. The final diagnosis in this case was hepatic angiomyolipoma (HAML) of the epithelioid type.

Figure 4 There are numerous focal capillaries, hemorrhage, and hemosiderin present within the lesion (hematoxylin-eosin, ×10).

Discussion

Due to the lack of obvious clinical features of HEAML, which is mostly detected through physical examination, diagnosis is challenging. HEAML has historically been regarded as a “benign” mesenchymal tumor. However, in 2000, Dalle et al. reported the first case of malignant HEAML, characterized by vascular invasion and recurrence with multiple liver metastases, along with suspected portal vein thrombosis occurring 5 months after primary tumor resection (4). Therefore, early diagnosis of HEAML is crucial, particularly with the rapid advancement of multimodal imaging, which offers greater diagnostic possibilities.

HEAML is common in middle-aged and elderly people, with female predilection. The ratio of men to women with the disease is approximately 1:5 (5). We utilized multimodal imaging to describe a 69-year-old female patient with a solitary mass in the right lobe of the liver.

By reviewing the past literature, we made some notable observations. In a past report, Aydin et al. suggested that HEAML was associated with tuberous sclerosis (6). Recent studies have described the diagnostic significance of dynamic contrast-enhanced CT and MR scans of lesions with early enhancement, sustained and delayed enhancement in the portal venous phase for HEAML and found that there are various enhancement modalities for HEAML (7,8). Because of the presence of a large number of thick-walled malformed blood vessels and blood sinuses in some tumors, it takes a longer time for the contrast medium to exit the extravascular space, so the tumor shows significant inhomogeneous enhancement in the arterial phase and continuous or delayed enhancement in the portal vein phase (9). In our case, the CT performance of HEAML was significantly enhanced in the arterial phase, slightly less intensified in the portal vein phase, and the delay phase. Further assessment was carried out using MIP to exhibit the strip enhancement vessel in the mass, which was called central vessel sign.

Li et al. did a study that included 113 patients with 122 pathologically confirmed HEAML, showed at enhanced MRI, hypointensity on T1-weighted, hyperintensity and heterogeneous signals on T2-weighted, hyperintensity on DWI, little or no fat component, heterogenous hyperenhancement, persistent enhancement, intra-tumor vessels, and outer rim would be helpful to diagnose HEAML (1). Previous literature showed most HEAML tumors were completely devoid of adipose tissue, so little or no fatty attenuation or tense was observed on CT or MRI images, which is a characteristic radiographic feature of HEAML compared with that of typical HAML (7). Out-phase and in-phase showed no significant attenuation in our case, indicating the lesion lack of fat component. Besides, the fat fraction value of liver parenchyma suggested that the patient has a fatty liver background. Approximately 10% of HEAML lesions have been found to present with feeding arteries, 30.0–33.3% with early draining veins, and 90% with intra-tumor vessels (10,11). Punctiform and filiform vessels could be seen in the lesion in the arterial phase, and halo enhancement was shown in the portal venous phase and delay phase in our study.

HEAML has potential malignant biological behavior (12), Song et al. found a case of intrapulmonary metastases at a year postoperative follow-up in their study (13).

HEAML should be differentiated from hypervascular tumors, such as HCC, FNH, and HA (Table 1). Most of the HCC showed a typical manifestation of “rapid filling and rapid excretion” (1), the same as “wash-in and wash-out enhancement” in our case. Cai et al. (8) reported that the pseudo-capsular of EAML appeared as a “peripherally decreasing strengthening margin”, due to the large number of tumor vessels contained in the tumor margin, it was significantly strengthened in the arterial phase and the contrast medium was contoured in the equilibrium phase. The “pseudo-capsular” sign of HEAML helps to differentiate it from the “pseudo-capsular” of HCC with equilibrium phase enhancement, and AFP has been widely used as a tool for HCC screening, diagnosis, monitoring, recurrence monitoring, and prognosis prediction, which is negative in HEAML (14). Typical focal hepatic nodular hyperplasia without pseudo-capsular, and delayed intensification with central fibrous scar reinforcement are easily distinguished from HEAML. HA predominantly occurs in young women and is frequently associated with a history of long-term oral contraceptive use. Imaging findings typically reveal faint enhancement in the arterial phase, followed by iso-intensity in the portal venous phase. Additionally, the tumor may demonstrate intratumoral hemorrhage, and fatty components can occasionally be identified.

New findings

In our case, we found some features. In the CT maximum cross-section of the lesion, the range of arterial enhancement was significantly larger than that of plain scan (Figure 1A,1B), and the boundary between the lesion and the surrounding liver tissue is not clear, which may be caused by perfusion disorder. We believed that the rich blood supply of the tumor confirmed by pathology, is the cause of perfusion disorder. The neoplastic tumor vessels caused a steal phenomenon to the surrounding liver parenchyma, which was manifested as transient wedge enhancement in the arterial phase. On the dynamic enhancement phase of the lesion in MRI, the surrounding showed a halo sign, this phenomenon may be caused by hemorrhage of peritumoral tortuous vascular, and it was confirmed by pathology that there were scattered hemorrhage foci. Furthermore, R2* sequence showed obviously high signal area, suggesting that there was hemosiderin deposition in the lesion, and the hyperintensity area coincided with the hypointensity area in the lesion of T2 sequence. The above manifestations indicate that there may be hemorrhagic lesions. We used gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) as the contrast medium for MRI enhancement. Gd-EOB-DTPA, a commonly used liver contrast medium, is manufactured by Bayer AG, a German company. It can be taken up by liver cells, excreted through the bile duct, and is also excreted through the kidney. Compared to other contrast media, it has an additional HBP. On HBP, the lesion showed hypointensity, indicating that there was no normal liver function tissue in the mass. Compared to CT contrast medium, which responded to the degree of blood supply, Gd-EOB-DTPA primarily responded to whether the mass had normal liver function, hence the difference in enhancement patterns between CT and MRI. We also used IDEAL IQ to reconstruct 6 phases, including in-phase, out-phase, water phase, fat phase, fat fraction and R2*. Among them, the in-phase, out-phase, and fat fraction are a good indication of the mild fatty liver background and lack of fat components in the lesion. R2* manifested the hemorrhage in the lesion. Interestingly, iron deposits are usually found at the margins of the lesion, suggesting that the abundant blood supply at the margins leads to hemorrhage. According to a recent report, HEAML has a certain malignant biological behavior, so it is necessary to identify possible metastases and regular postoperative follow-up imaging. A systematic evaluation of the imaging features of the lesions can greatly reduce the misdiagnosis rate, but biopsy, when necessary, is the gold standard for confirmation. We hope that this case report will make future researchers more cautious in the diagnosis of HEAML and give them some inspiration.

Limitation and trends

Current studies on HEAML often face the challenge of a paucity of cases. This limitation is also evident in our research, and even the rare multicase studies available are typically constrained by their single-center nature. We therefore suggest that future studies focusing on HEAML should aim for multicase, multicenter designs, thereby enhancing the generalizability and persuasive power of their imaging characteristics. Furthermore, most reported cases noted that patients failed to undergo regular imaging follow-ups postoperatively. This practice is not recommended for hepatocellular tumors with potential malignancy. Therefore, future clinical practice should prioritize improving patient awareness regarding follow-up adherence. While assessing prognosis, more imaging correlates predictive of outcome can be retrieved, contributing to refined prognostic evaluations.

As HEAML’s imaging features closely resemble those of HCC, patients are frequently misdiagnosed and undergo resection surgery initially. Surgical resection is recommended for this potentially malignant tumor. Concerning postoperative management, as previously stated, it is crucial to emphasize the importance of follow-up care to patients. Regularly scheduled imaging examinations should be conducted to monitor for any signs of tumor recurrence.

Conclusions

In summary, the imaging manifestations of HEAML overlap with some tumor characteristics, but certain signs can offer significant value for differential diagnosis. Particularly with the aid of multimodal imaging, most HEAML signs can be more readily identified. Analysis of the case based on multimodal imaging findings revealed that both the central vessel sign on MIP and the discontinuous pseudo-capsule on MRI exhibited typical characteristics of HEAML. The IDEAL IQ serves as a better tool for analyzing the composition of HEAML, where the absence of attenuation on in-phase and out-phase images indicates the absence of fat within the lesion, and the ring of hyperintensity on R2* also suggests that hemorrhage within the lesion is predominantly peripheral.

While pathology remains the gold standard for diagnosing HEAML, the non-invasive nature of CT and MRI has made them indispensable examinations for the majority of tumor patients. The emergence of multimodal imaging, encompassing CT and multi-sequence MRI, represents a growing trend in liver tumor research. This approach holds promise for facilitating early diagnosis and enhancing follow-up procedures for HEAML.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-837/rc

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-837/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-837/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Junhao L, Hongxia Z, Jiajun G, et al. Hepatic epithelioid angiomyolipoma: magnetic resonance imaging characteristics. Abdom Radiol (NY) 2023;48:913-24. [Crossref] [PubMed]
2. Kamimura K, Nomoto M, Aoyagi Y. Hepatic angiomyolipoma: diagnostic findings and management. Int J Hepatol 2012;2012:410781. [Crossref] [PubMed]
3. Yang CY, Ho MC, Jeng YM, et al. Management of hepatic angiomyolipoma. J Gastrointest Surg 2007;11:452-7. [Crossref] [PubMed]
4. Dalle I, Sciot R, de Vos R, et al. Malignant angiomyolipoma of the liver: a hitherto unreported variant. Histopathology 2000;36:443-50. [Crossref] [PubMed]
5. Mao JX, Teng F, Liu C, et al. Two case reports and literature review for hepatic epithelioid angiomyolipoma: Pitfall of misdiagnosis. World J Clin Cases 2019;7:972-83. [Crossref] [PubMed]
6. Aydin H, Magi-Galluzzi C, Lane BR, et al. Renal angiomyolipoma: clinicopathologic study of 194 cases with emphasis on the epithelioid histology and tuberous sclerosis association. Am J Surg Pathol 2009;33:289-97. [Crossref] [PubMed]
7. Ji JS, Lu CY, Wang ZF, et al. Epithelioid angiomyolipoma of the liver: CT and MRI features. Abdom Imaging 2013;38:309-14. [Crossref] [PubMed]
8. Cai PQ, Wu YP, Xie CM, et al. Hepatic angiomyolipoma: CT and MR imaging findings with clinical-pathologic comparison. Abdom Imaging 2013;38:482-9. [Crossref] [PubMed]
9. Wu ZJ, Hua H, Chen JJ, et al. CT characteristics of hepatic epithelial angiomyolipoma. Chinese Journal of Medical Imaging Technology 2013;29:84-87.
10. Xu PJ, Shan Y, Yan FH, et al. Epithelioid angiomyolipoma of the liver: cross-sectional imaging findings of 10 immunohistochemically-verified cases. World J Gastroenterol 2009;15:4576-81. [Crossref] [PubMed]
11. Liu W, Wang J, Huang Q, et al. Comparison of MRI Features of Epithelioid Hepatic Angiomyolipoma and Hepatocellular Carcinoma: Imaging Data From Two Centers. Front Oncol 2018;8:600. [Crossref] [PubMed]
12. Xie L, Jessurun J, Manivel JC, et al. Hepatic epithelioid angiomyolipoma with trabecular growth pattern: a mimic of hepatocellular carcinoma on fine needle aspiration cytology. Diagn Cytopathol 2012;40:639-50. [Crossref] [PubMed]
13. Song X, Xu SL, Xiao WB CT. Chinese Journal of Medical Imaging Technology 2016;32:87-90.
14. Nomura F, Ohnishi K, Tanabe Y. Clinical features and prognosis of hepatocellular carcinoma with reference to serum alpha-fetoprotein levels. Analysis of 606 patients. Cancer 1989;64:1700-7. [Crossref] [PubMed]